ArticlebioRxiv : the preprint server for biology2025
Identify Alzheimer's disease subtypes and markers from multi-omic data of human brain and blood with a subspace merging algorithm.
Ziyan Song, Xiaoqing Huang, Asha Jacob Jannu, Travis S Johnson, Jie Zhang, Kun Huang
Abstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 · The recordCorrections and comments
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5 · Who and what moneyAuthors and funding
6 authors.
Ziyan SongDepartment of Biostatistics and Health Data Science, Indiana University School of Medicine, IN, USA.ORCID 0009-0000-5679-1751 Xiaoqing HuangDepartment of Biostatistics and Health Data Science, Indiana University School of Medicine, IN, USA.
Asha Jacob JannuDepartment of Bioengineering and Informatics, Indiana University Schoold of Medicine, IN, USA.
Travis S JohnsonDepartment of Biostatistics and Health Data Science, Indiana University School of Medicine, IN, USA.
Jie ZhangDepartment of Biostatistics and Health Data Science, Indiana University School of Medicine, IN, USA.
Kun HuangDepartment of Biostatistics and Health Data Science, Indiana University School of Medicine, IN, USA.
Funding
Vascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Richard B. LIPTON · 1985 to 2026
$73.9MStructural Biology CoreU54AG065181 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI Alan D. Palkowitz · 2019 to 2026
$61.3MAlzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MSUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MTHE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9MResearch Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5MIntegrative Network Biology Approaches to Identify, Characterize and Validate Molecular Subtypes in Alzheimer's DiseaseU01AG046170 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WANG, MINGHUI, ZHANG, BIN · 2013 to 2022
$26.0MRush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7MIntegrating the exposome and methylome to inform brain molecular changes in ADRD across established diverse cohorts.U01AG046139 · NIA · UNIVERSITY OF FLORIDA · PI ERTEKIN-TANER, NILUFER, FUNK, CORY · 2013 to 2022
$24.6MTox-AD: a new multi-institute tri-consortium data resource in the AD Knowledge PortalU24AG061340 · NIA · SAGE BIONETWORKS · PI Laura Michelle Heath, Susheel Varma · 2018 to 2026
$24.6MNIA NIH HHS P01 AG003949NIA NIH HHS P01 AG017216NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG072975NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG025711NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG018023NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG036042NIA NIH HHS R01 AG036836NIA NIH HHS R01 AG048015NIA NIH HHS R21 AG075541NIA NIH HHS RC2 AG036547NIA NIH HHS RF1 AG057440NIA NIH HHS RF1 AG057473NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG046161NIA NIH HHS U01 AG046170NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG061357NIA NIH HHS U24 AG061340NIA NIH HHS U54 AG065181NINDS NIH HHS R01 NS080820NINDS NIH HHS U24 NS072026
6 · The paper itselfAbstract
Identifying Alzheimer's disease (AD) subtypes is essential for AD diagnosis and treatment. We integrated multiomics data from brain tissues of the ROSMAP and MSBB studies using a subspace merging algorithm and identified two AD patient clusters with notable cognitive and AD pathology differences. Analysis of differentially expressed genes (DEGs) in brain and blood samples pinpointed the LDLR gene as a potential blood biomarker linked to brain gene expression changes. Furthermore, we conducted PheWAS analysis on All of Us Project's EHR and WGS dataset for 105 eQTLs associated with the DEGs and revealed significant associations between these eQTLs and several phenotypes, shedding light on potential regulatory roles of these genes in diverse physiological processes. Our study successfully integrated multiomics data and proposes LDLR as a candidate blood biomarker for AD subtyping. The identified phenotypic signatures provide valuable insights on molecular mechanisms underlying AD heterogeneity, paving the way for personalized AD treatment.
Indexed as
Alzheimer’s DiseaseMulti-omcisReal-world DataSubspace merging algorithmSubtyping
Identifiers
PMID40654912
PMCPMC12247635
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